Chitosan-enhanced sensitivity of mercaptoundecanoic acid (MUA)- capped gold nanorod based localized surface plasmon resonance (LSPR) biosensor for detection of alpha-synuclein oligomer biomarker in parkinson's disease.

Alpha-synuclein oligomers play a crucial role in the early diagnosis of Parkinson's disease (PD). In this study, a mercaptoundecanoic acid (MUA)-capped gold nanorod (GNR)-coated and chitosan (CH)-immobilized fiber optic probe has shown considerable sensitivity of its detection. The proposed U-shaped fiber optic biosensor based on localized surface plasmon resonance (LSPR) was applied to detect α-syn oligomer (OA) biomarker. By analyzing OA concentrations, the biosensor achieved a limit of detection of (LOD) 11 pM within the concentration range of 10-100 pM and the sensitivity value was found as 502.69 Δλ/RIU. Upon analysis of the CV% (coefficient of variation) and accuracy/recovery values, it is revealed that the sensor successfully fulfilled the criteria for success, displaying accuracy/recovery values within the range of 80%-120% and CV% values below 20%. This sensor presents significant advantages, including high sensitivity, specificity, and ability to detect very low concentrations of OA. In conclusion, the suggested U-shaped fiber optic biosensor has the potential to be valuable in the early detection of PD from a clinical perspective.

In Situ Photoreversible Tuning of Chemical Interface Damping in Single Gold Nanorods Through Cucurbit[8]uril-Based Host-Guest Interactions.

Chemical interface damping (CID) is a recently proposed plasmon-damping pathway based on the interfacial hot-electron transfer from metal to adsorbate molecules. However, the in situ reversible tuning of CID in single gold nanorods (AuNRs) has remained a considerable challenge. In this study, we used total internal reflection scattering microscopy and spectroscopy to investigate the CID induced by p-aminoazobenzene (p-AAB), which has fast photoisomerization characteristics, attached to single AuNRs. We demonstrated the in situ reversible tuning of CID in single AuNRs by switching between ultraviolet (UV, 365 nm) and visible (vis, 465 nm) irradiation to induce photoresponsive structural conversions between the cis and trans forms of p-AAB in ethanol, leading to different lowest unoccupied molecular orbital (LUMO) energies for both forms. The localized surface plasmon resonance (LSPR) line width was wide under vis irradiation but narrow under UV irradiation, indicating that hot electrons are more efficiently transferred to trans-p-AAB with a low LUMO energy level. We further investigated the in situ photoreversible tuning of CID by manipulating supramolecular host-guest interactions between cucurbit[8]uril (CB[8]) and p-AAB in the single AuNRs. Additionally, real-time in situ reversible tuning of CID in single AuNRs was achieved through photonic switching of the cis-trans forms of p-AAB inside CB[8]. The LSPR line width was narrow under vis irradiation but gradually widened under UV irradiation before narrowing again upon returning to vis irradiation, unlike the case with p-AAB only. These results can be ascribed to the fact that cis-p-AAB completely encapsulated within CB[8] in water is thermodynamically more favorable than trans-p-AAB. Therefore, we have discovered a new strategy for tuning the CID by performing p-AAB photoisomerization and adjusting the wavelength of incident light in single AuNRs. In addition, this study demonstrates that CID can be effectively applied to the development of biosensors to detect guest molecules and their structural changes inside the cavity of CB[8] in single AuNRs.

Electrostatically self-assembled gold nanorods with sulfated hyaluronic acid for targeted photothermal therapy for CD44-positive tumors.

Gold nanorods (GNR) produce heat upon irradiation with near-infrared light, enabling a tumor-targeted photothermal therapy. In this study, we prepared GNR coated with sulfated hyaluronic acid (sHA) with a binding affinity for CD44 via electrostatic interactions to deliver GNR to tumors efficiently and stably, and evaluated their usefulness for photothermal therapy. Cationic GNR modified with trimethylammonium groups electrostatically interacted with native HA or sHA with varying degrees of sulfation to form complexes. While GNR/HA was unstable in saline, GNR/sHA maintained the absorbance peak in the near-infrared region, particularly for GNR/sHA with higher degrees of sulfation. GNR/sHA exhibited an intense photothermal effect upon irradiation with near-infrared light. Furthermore, in vitro and in vivo studies revealed that GNR coated with sHA containing approximately 1.2 sulfated groups per HA unit could accumulate in CD44-positive tumors via an HA-specific pathway. These findings indicate the effectiveness of GNR/sHA as a tumor-targeted photothermal therapeutic agent.

Lipid-coated gold nanorods for photoimmunotherapy of primary breast cancer and the prevention of metastasis.

Nanomedicines hold promise for the treatment of various diseases. However, treating cancer metastasis remains highly challenging. In this study, we synthesized gold nanorods (AuNRs) containing (α-GC), an immune stimulator, for the treatment of primary cancer, metastasis, and recurrence of the cancer. Therefore, the AuNR were coated with lipid bilayers loaded with α-GC (α-LA). Upon irradiation with 808 nm light, α-LA showed a temperature increase. Intra-tumoral injection of α-LA in mice and local irradiation of the 4T1 breast cancer tumor effectively eliminated tumor growth. We found that the presence of α-GC in α-LA activated dendritic cells and T cells in the spleen, which completely blocked the development of lung metastasis. In mice injected with α-LA for primary breast cancer treatment, we observed antigen-specific T cell responses and increased cytotoxicity against 4T1 cells. We conclude that α-LA is promising for the treatment of both primary breast cancer and its metastasis.

4D Printed Protein-AuNR Nanocomposites with Photothermal Shape Recovery.

4D printing is the 3D printing of objects that change chemically or physically in response to an external stimulus over time. Photothermally responsive shape memory materials are attractive for their ability to undergo remote activation. While photothermal methods using gold nanorods (AuNRs) have been used for shape recovery, 3D patterning of these materials into objects with complex geometries using degradable materials has not been addressed. Here, we report on the fabrication of 3D printed shape memory bioplastics with photo-activated shape recovery. Protein-based nanocomposites based on bovine serum albumin (BSA), poly (ethylene glycol) diacrylate and gold nanorods were developed for vat photopolymerization. These 3D printed bioplastics were mechanically deformed under high loads, and the proteins served as mechanoactive elements that unfolded in an energy-dissipating mechanism that prevented fracture of the thermoset. The bioplastic object maintained its metastable shape-programmed state under ambient conditions. Subsequently, up to 99% shape recovery was achieved within 1 min of irradiation with near-infrared light. Mechanical characterization and small angle X-ray scattering (SAXS) analysis suggest that the proteins mechanically unfold during the shape programming step and may refold during shape recovery. These composites are promising materials for the fabrication of biodegradable shape-morphing devices for robotics and medicine.

An oleanic acid decorated gold nanorod for highly efficient inhibition of hemagglutinin and visible rapid detection of the influenza virus.

Accurate diagnosis and effective antiviral treatments are urgently needed for the prevention and control of flu caused by influenza viruses. In this study, a novel oleanic acid (OA) functionalized gold nanorod OA-AuNP was prepared through a convenient ligand-exchange reaction. As hemagglutinin (HA) on the viral surface binds strongly to the multiple OA molecules on the surface of the nanoparticle, the prepared OA-AuNP was found to exhibit potent antiviral activity against a wide range of influenza A virus strains. Furthermore, the change in color resulting from the specific binding between HA and OA and the resultant aggregation of the OA-AuNP can be visually observed or measured by UV-vis spectra with a detection limit of 2 and 0.18 hemagglutination units (HAU), respectively, which is comparable to the commercially available influenza colloid gold rapid diagnostic kits. These findings demonstrate the potential of the OA-AuNP for the development of novel multivalent antiviral conjugates and the diagnosis of influenza virus.

Chemo-photothermal therapy of chitosan/gold nanorod clusters for antibacterial treatment against the infection of planktonic and biofilm MRSA.

Bacterial infections trigger inflammation and impede the closure of skin wounds. The misuse of antibiotics exacerbates skin infections by generating multidrug-resistant bacteria. In this study, we developed chemo-photothermal therapy (chemo-PTT) based on near-infrared (NIR)-irradiated chitosan/gold nanorod (GNR) clusters as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents. The nanocomposites exhibited an average size of 223 nm with a surface charge of 36 mV. These plasmonic nanocomposites demonstrated on-demand and rapid hyperthermal action under NIR. The combined effect of positive charge and PTT by NIR-irradiated nanocomposites resulted in a remarkable inhibition rate of 96 % against planktonic MRSA, indicating a synergistic activity compared to chitosan nanoparticles or GNR alone. The nanocomposites easily penetrated the biofilm matrix. The combination of chemical and photothermal treatments by NIR-stimulated clusters significantly damaged the biofilm structure, eradicating MRSA inside the biomass. NIR-irradiated chitosan/GNR clusters increased the skin temperature of mice by 13 °C. The plasmonic nanocomposites induced negligible skin irritation in vivo. In summary, this novel nanosystem demonstrated potent antibacterial effects against planktonic and biofilm MRSA, showcasing the possible efficacy in treating skin infections.

PDADMAC/Alginate-Coated Gold Nanorod For Eradication of Staphylococcus Aureus Biofilms.

Introduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections. Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied. Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy. Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.

Combined Photothermal Therapy and Cancer Immunotherapy by Immunogenic Hollow Mesoporous Silicon-Shelled Gold Nanorods.

Hyperthermia can be integrated with tumor-killing chemotherapy, radiotherapy and immunotherapy to give rise to an anti-tumor response. To this end, a nano-delivery system is built, which can connect hyperthermia and immunotherapy. On this basis, the impact of such a combination on the immune function of dendritic cells (DCs) is explored. The core of this system is the photothermal material gold nanorod (GNR), and its surface is covered with a silica shell. Additionally, it also forms a hollow mesoporous structure using the thermal etching approach, followed by modification of targeted molecule folic acid (FA) on its surface, and eventually forms a hollow mesoporous silica gold nanorod (GNR@void@mSiO2) modified by FA. GNR@void@mSiO2-PEG-FA (GVS-FA) performs well in photothermal properties, drug carriage and release and tumor targeting performance. Furthermore, the thermotherapy of tumor cells through in vitro NIR irradiation can directly kill tumor cells by inhibiting proliferation and inducing apoptosis. GVS-FA loaded with imiquimod (R837) can be used as a adjuvant to enhance the immune function of DCs through hyperthermia.

Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells.

Calcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA-GNR) conjugated glutamic acid developed in the study was used as a nano-bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA-GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.

Ameliorated Skin Inflammation through the Synergistic Effect of Gold Nanorod-Dexamethasone and Photothermal Therapy.

Psoriasis, a prevalent chronic inflammatory skin ailment affecting approximately 2-3% of the global population, is characterized by persistent symptoms. Dexamethasone, a primary corticosteroid for treating psoriasis, demonstrates notable efficacy; however, its limited skin permeation results in documented adverse effects. To address this, the presented study employed a novel strategy to conjugate gold nanorod and dexamethasone and evaluate their potential for mitigating psoriatic inflammation using an imiquimod-induced mouse model and human skin cells. Our findings revealed enhanced cutaneous penetration of gold nanorod and dexamethasone conjugates compared with that of dexamethasone, owing to superior skin penetration. Gold nanorod and dexamethasone conjugates demonstrated an optimal pharmacological impact at minimal dosages without toxicity during extended use. To further enhance the effectiveness of gold nanorod and dexamethasone conjugates, 808 nm near-infrared laser irradiation, which reacts to gold, was additionally applied to achieve thermal elevation to expedite drug skin penetration. Supplementary laser irradiation at 808 nm significantly ameliorated psoriatic symptoms following deep gold nanorod and dexamethasone conjugates penetration. This corresponded with restored peroxisome proliferator-activated receptor-γ levels and accelerated dexamethasone release from the gold nanorod and dexamethasone conjugates complex. These findings highlight the potential of gold nanorod and dexamethasone conjugates to enhance drug penetration through dermal layers, thereby aiding psoriasis treatment. Moreover, its compatibility with photothermal therapy offers prospects for novel therapeutic interventions across various inflammatory skin disorders.

Size Dependence of Gold Nanorods for Efficient and Rapid Photothermal Therapy.

In recent years, gold nanomaterials have become a hot topic in photothermal tumor therapy due to their unique surface plasmon resonance characteristics. The effectiveness of photothermal therapy is highly dependent on the shape and size of gold nanoparticles. In this work, we investigate the photothermal therapeutic effects of four different sizes of gold nanorods (GNRs). The results show that the uptake of short GNRs with aspect ratios 3.3-3.5 by cells is higher than that of GNRs with aspect ratios 4-5.5. Using a laser with single pulse energy as low as 28 pJ laser for 20 s can induce the death of liver cancer cells co-cultured with short GNRs. Long GNRs required twice the energy to achieve the same therapeutic effect. The dual-temperature model is used to simulate the photothermal response of intracellular clusters irradiated by a laser. It is found that small GNRs are easier to compact because of their morphological characteristics, and the electromagnetic coupling between GNRs is better, which increases the internal field enhancement, resulting in higher local temperature. Compared with a single GNR, GNR clusters are less dependent on polarization and wavelength, which is more conducive to the flexible selection of excitation laser sources.

Applications of the Photocatalytic and Photoacoustic Properties of Gold Nanorods in Contrast-Enhanced Ultrasound and Photoacoustic Imaging.

The applications of ultrasound imaging are often limited due to low contrast, which arises from the comparable acoustic impedance of normal tissues and disease sites. To improve the low contrast, we propose a contrast agent called gas-generating laser-activatable nanorods for contrast enhancement (GLANCE), which enhances ultrasound imaging contrast in two ways. First, GLANCE absorbs near-infrared lasers and generates nitrogen gas bubbles through the photocatalytic function of gold nanorods and photolysis of azide compounds. These gas bubbles decrease the acoustic impedance and highlight the injection site from the surrounding tissues. Second, GLANCE exhibits photoacoustic properties owing to the gold nanorods that emit photoacoustic signals upon laser irradiation. Additionally, GLANCE offers several benefits for biomedical applications such as nanometer-scale size, adjustable optical absorption, and biocompatibility. These distinctive features of GLANCE would overcome the limitations of conventional ultrasound imaging and facilitate the accurate diagnosis of various diseases.

Mesoporous Silica-Layered Gold Nanorod Core@Silver Shell Nanostructures for Intracellular SERS Imaging and Phototherapy.

Precision diagnosis-guided efficient treatment is crucial to extending the lives of cancer patients. The integration of surface-enhanced Raman scattering (SERS) imaging and phototherapy into a single nanoplatform has been considered a more accurate diagnosis and treatment strategy for cancer nanotheranostics. Herein, we constructed a new type of mesoporous silica-layered gold nanorod core@silver shell nanostructures loaded with methylene blue (GNR@Ag@mSiO2-MB) as a multifunctional nanotheranostic agent for intracellular SERS imaging and phototherapy. The synthesized GNR@Ag@mSiO2-MB nanostructures possessed a uniform core-shell structure, strong near-infrared (NIR) absorbance, photothermal conversion efficiency (65%), dye loading ability, SERS signal, and Raman stability under phototherapy conditions. Under single 785 nm NIR laser irradiation, the intracellular GNR@Ag@mSiO2-MB nanostructures were dramatically decreased to <9%, which showed excellent photothermal and photodynamic effects toward cancer cell killing, indicating that the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) of the GNR@Ag@mSiO2-MB nanostructures could greatly enhance the therapeutic efficacy of cancer cell death. GNR@Ag@mSiO2-MB nanostructures demonstrated a strong Raman signal at 450 and 502 cm-1, corresponding to the δ(C-N-C) mode, suggesting that the Raman bands of GNR@Ag@mSiO2-MB nanostructures were more efficient to detect CT-26 cell SERS imaging with high specificity. Our results indicate that GNR@Ag@mSiO2-MB nanostructures offer an excellent multifunctional nanotheranostic platform for SERS imaging and synergistic anticancer phototherapy in the future.

A simulation study on the radiosensitization properties of gold nanorods.

Objective. Gold nanorods (GNRs) have emerged as versatile nanoparticles with unique properties, holding promise in various modalities of cancer treatment through drug delivery and photothermal therapy. In the rapidly evolving field of nanoparticle radiosensitization (NPRS) for cancer therapy, this study assessed the potential of gold nanorods as radiosensitizing agents by quantifying the key features of NPRS, such as secondary electron emission and dose enhancement, using Monte Carlo simulations.Approach. Employing the TOPAS track structure code, we conducted a comprehensive evaluation of the radiosensitization behavior of spherical gold nanoparticles and gold nanorods. We systematically explored the impact of nanorod geometry (in particular size and aspect ratio) and orientation on secondary electron emission and deposited energy ratio, providing validated results against previously published simulations.Main results. Our findings demonstrate that gold nanorods exhibit comparable secondary electron emission to their spherical counterparts. Notably, nanorods with smaller surface-area-to-volume ratios (SA:V) and alignment with the incident photon beam proved to be more efficient radiosensitizing agents, showing superiority in emitted electron fluence. However, in the microscale, the deposited energy ratio (DER) was not markedly influenced by the SA:V of the nanorod. Additionally, our findings revealed that the geometry of gold nanoparticles has a more significant impact on the emission of M-shell Auger electrons (with energies below 3.5 keV) than on higher-energy electrons.Significance. This research investigated the radiosensitization properties of gold nanorods, positioning them as promising alternatives to the more conventionally studied spherical gold nanoparticles in the context of cancer research. With increasing interest in multimodal cancer therapy, our findings have the potential to contribute valuable insights into the perspective of gold nanorods as effective multipurpose agents for synergistic photothermal therapy and radiotherapy. Future directions may involve exploring alternative metallic nanorods as well as further optimizing the geometry and coating materials, opening new possibilities for more effective cancer treatments.

Development of a peptide microarray-based metal-enhanced fluorescence assay for ultrasensitive detection of multiple matrix metalloproteinase activities by using a gold nanorod-polymer substrate.

Matrix metalloproteinases (MMPs) are attractive biomarkers for cancer diagnosis and treatment, while it is still a challenge to precise analysis of MMP activities owing to their very low abundance in the biological samples, especially at the early stages of tumors. Herein, a peptide microarray-based metal-enhanced fluorescence assay (PMMEFA) is proposed to simultaneously detect MMP-1, -2, -3, -7, -9, and -13 activities. The assay involves immobilization of Förster resonance energy transfer dye pair decorated peptides (FRET-peptides) on a poly(glycidyl methacrylate-co-2-hydroxyethyl methacrylate) coated gold nanorod modified glass slide (GNR@P(GMA-HEMA)). To fabricate the GNR@P(GMA-HEMA) slide, GNRs are self-assembled onto an aminated glass slide, and a polymer brush (P(GMA-HEMA)) is grown through a surface-initiated atom transfer radical polymerization reaction (SI-ATRP). Upon the addition of MMPs, the FRET pairs are broken due to the specific cleavage of FRET-peptides by enzymes, resulting in the recovery of fluorescence signals and further enhancement by the MEF of GNRs. The fluorescence recovery degree provides a direct indicator for MMP activity. The PMMEFA exhibits excellent sensitivity, which enables to detect MMP-1, -2, -3, -7, -9, and -13 activities, with low limits of detection (LODs) of 1.7 fg mL-1, 0.3 fg mL-1, 2.0 fg mL-1, 1.8 fg mL-1, 2.2 fg mL-1 and 14.0 fg mL-1, respectively. To substantiate the practicability of PMMEFA, MMP activities were measured in a range of matrices, encompassing cell culture medium, serum, and tumor tissue homogenate, and MMP activities can be detected only in 0.15 µL serum and 0.025 mg tumor tissue.

Drug-Free Antimicrobial Nanomotor for Precise Treatment of Multidrug-Resistant Bacterial Infections.

Manufacturing heteronanostructures with specific physicochemical characteristics and tightly controllable designs is very appealing. Herein, we reported NIR-II light-driven dual plasmonic (AuNR-SiO2-Cu7S4) antimicrobial nanomotors with an intended Janus configuration through the overgrowth of copper-rich Cu7S4 nanocrystals at only one high-curvature site of Au nanorods (Au NRs). These nanomotors were applied for photoacoustic imaging (PAI)-guided synergistic photothermal and photocatalytic treatment of bacterial infections. Both the photothermal performance and photocatalytic activity of the nanomotors are dramatically improved owing to the strong plasmon coupling between Au NRs and the Cu7S4 component and enhanced energy transfer. The motion behavior of nanomotors promotes transdermal penetration and enhances the matter-bacteria interaction. More importantly, the directional navigation and synergistic antimicrobial activity of the nanomotors could be synchronously driven by NIR-II light. The marriage of active motion and enhanced antibacterial activity resulted in the expected good antibacterial effects in an abscess infection mouse model.

Effect of Polymeric Ligand Grafting Region on Confined Assembly of Gold Nanorods in cylindrical nanopores.

The grafting region of polymeric ligands exhibit a significant influence on the assembly behavior of polymer tethered gold nanorods (AuNRs) in confined space. In this work, the effect of core size, molecular weight and grafting region of ligands on the assembly structure in cylindrical nanopores was investigated. It is found that polystyrene end-tethered AuNR (AuNR@End-PS) exhibits a dumbbell-like shape, while the AuNR with PS tethered on the entire surface (AuNR@Full-PS) shows a rod-like morphology that gradually transforms into a spherical shape as the molecular weight increases. AuNR@End-PS is affected by the special steric hindrance at both ends, and prefers to form special structures such as inclination arrangement, whereas AuNR@Full-PS prefers to be arranged shoulder-to-shoulder in a chain-like assembly. The confinement effect was studied as well by varying the diameter of pores. The results show that the nanoparticles prefer to arrange into a regular and ordered assembly structure in the strong confinement spaces. Under the synergy of confined spaces and ligands at both ends, the AuNRs@End-PS are more likely to form a tilted order-assembly structure. The results of this work could provide new ideas and guidance for the preparation of ordered assembly of AuNRs with novel structures.

Dual Targeted Delivery of Liposomal Hybrid Gold Nano-Assembly for Enhanced Photothermal Therapy against Lung Carcinomas.

The delivery and accumulation of therapeutic drugs into cancer cells without affecting healthy cells are a major challenge for antitumor therapy. Here, we report the synthesis of a liposomal hybrid gold nano-assembly with enhanced photothermal activity for lung cancer treatment. The core components of the nano-assembly include gold nanorods coated with a mesoporous silica shell that offers an excellent drug-loading surface for encapsulation of doxorubicin. To enhance the photothermal capacity of nano-assembly, IR 780 dye was loaded inside a thermo-sensitive liposome, and then, the core nano-assembly was wrapped within the liposome, and GE-11 peptide and folic acid were conjugated onto the surface of the liposome to give the final nano-assembly [(GM@Dox) LI]-PF. The dual targeting approach of [(GM@Dox) LI]-PF leads to enhanced cellular uptake and improves the accumulation of nano-assemblies in cancer cells that overexpress the epidermal growth factor receptor and folate. The exposure of near-infrared laser irradiation can trigger photothermal-induced structural disruption of the nano-assembly, which allows for the precise and controllable release of Dox at targeted sites. Additionally, chemo-photothermal therapy was shown to be 11 times more effective in cancer cell treatment when compared to Dox alone. Our systematic study suggests that the nano-assemblies facilitate the cancer cells undergoing apoptosis via an intrinsic mitochondrial pathway that can be directly triggered by the chemo-photothermal treatment. This study offers an appealing candidate that holds great promise for synergistic cancer treatment.

CXC Chemokine Receptor Type 4 Antagonistic Gold Nanorods Induce Specific Immune Responses and Long-Term Immune Memory to Combat Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly challenging in its treatment because of the lack of the targeted markers. TNBC patients are not able to acquire benefits from endocrine therapy and targeted therapy except for chemotherapy. CXCR4 is highly expressed on TNBC cells that mediated the tumor cell metastasis as well as proliferation by the response of its ligand CXCL12, therefore holding promising potential of a candidate target for the treatment. In this work, a novel conjugate of CXCR4 antagonist peptide E5 and gold nanorods was fabricated (AuNRs-E5), which was applied to murine breast cancer tumor cells and an animal model, aiming to induce endoplasmic reticulum stress by endoplasmic reticulum-targeted photothermal immunological effects. Results showed that AuNRs-E5 could induce much more generation of damage-related molecular patterns in 4T1 cells under laser irradiation than AuNRs, which significantly promoted the maturation of dendritic cells and stimulated systematic anti-tumor immune responses by enhancing the infiltration of CD8+T cells into the tumor and tumor-draining lymph node, downregulating the regulatory T lymphocytes, and upregulating M1 macrophages in tumors, reversing the microenvironment from "cold" tumors to "hot" tumors. The administration of AuNRs-E5 with laser irradiation not only inhibited the tumor growth significantly but also exerted specific long immune responses to the triple-negative breast cancer tumor cells, which led to the prolonged survival of the mice and the specific immunological memory.